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Severe COVID-19 was associated with elevated risks for depression and serious mental illness months after infection, especially among unvaccinated people, a cohort study involving more than 18 million individuals in the U.K. found.

Compared to the period before a COVID infection or to individuals without an infection, those hospitalized for COVID had substantially higher risks for depression in the 4 weeks after admission, both in the pre-vaccine era (adjusted hazard ratio [aHR] 16.3, 95% CI 15.6-17.0) and among unvaccinated (aHR 15.6, 95% CI 13.9-17.4) and vaccinated (aHR 12.9, 95% CI 12.0-14.0) individuals in the vaccine era. In all three groups, the risk for depression remained elevated up to a year later.

Similarly, elevated risks for serious mental illness were observed among hospitalized patients in the 4 weeks after a COVID diagnosis, reported Jonathan Sterne, PhD, of the University of Bristol in England, and colleagues in :

• Pre-vaccine era: aHR 9.71 (95% CI 8.80-10.7)
• Unvaccinated: aHR 8.75 (95% CI 7.01-10.9)
• Vaccinated: aHR 6.52 (95% CI 5.36-7.93)

Rates of most mental illnesses examined -- including anxiety, post-traumatic stress disorder, eating disorders, addiction, and self-harm -- were higher in the first 4 weeks after a COVID hospitalization.

"The main surprise was that the association of COVID-19 with subsequent mental ill-health appeared restricted to severe COVID-19 that led to hospitalization," Sterne told MedPage Today. "There was little association of COVID-19 that did not lead to hospitalization with subsequent mental ill health."

Serious mental illness was a composite of schizophrenia, schizoaffective disorder, bipolar disorder, and psychotic depression.

Vaccination may attenuate adverse effects of COVID on mental illnesses, the authors posited. "Potential mechanisms include reduced systemic inflammation and psychological benefits of vaccination, such as reduced concern about COVID-19 and increased social engagement," they wrote.

"The main benefit of COVID-19 vaccination is that it provides substantial protection against severe COVID-19. Therefore, our findings underscore the importance of COVID-19 vaccination, particularly in groups at highest risk of severe COVID-19," Sterne emphasized.

"Serious mental illnesses are associated with more intensive healthcare needs and longer-term health and other adverse effects, and so longer-term monitoring for onset of new mental illnesses among patients hospitalized because of COVID-19 may be justified," he added.

Regardless of whether patients with COVID were hospitalized, in the pre-vaccine era the overall risk of depression in the 4 weeks after infection was 93% higher (aHR 1.93, 95% CI 1.88-1.98) than before or without COVID. The overall risk of developing serious mental illness was 49% higher (aHR 1.49, 95% CI 1.41-1.57). Among those who remained unvaccinated, the overall risks of depression (aHR 1.79, 95% CI 1.68-1.90) and serious mental illness (aHR 1.45, 95% CI 1.27-1.65) were also elevated.

Incidence of depression up to 28 weeks later and of serious mental illness across all time periods was greater in people 60 years and older, which may reflect increased risk for severe disease as well as anxiety about severe outcomes, the authors pointed out.

Of note, incidence of mental illnesses remained elevated for more than 28 weeks after a COVID-19 diagnosis. The estimated excess risk of depression at 28 weeks after COVID was 1,033 per 100,000 people in the pre-vaccine era and 1,008 per 100,000 in the unvaccinated group, whereas the risk among vaccinated people was less than half that, at 451 per 100,000.

The trend for serious mental illness at 28 weeks was similar, with an estimated excess risk of 235 and 209 per 100,000 in the pre-vaccine era and among the unvaccinated, respectively, versus 53 per 100,000 in the vaccinated group.

The study analyzed data from three cohorts during the pre-vaccine (January 2020 to June 2021) and vaccine eras (June to December 2021; the Delta variant period):

• 18,648,606 adults during the pre-vaccine era, of whom 1,012,335 had a confirmed COVID diagnosis
• 14,035,286 vaccinated adults, of whom 866,469 had a confirmed COVID diagnosis
• 3,242,215 unvaccinated adults, of whom 149,745 had a confirmed COVID diagnosis

The average ages of the pre-vaccine and vaccinated cohorts were 49 and 53, respectively, and about half were female. The average age of the unvaccinated cohort was 35 years and about 42% were female. Diagnoses of COVID were confirmed by test results, by a general practitioner, or from hospital or death records.

The authors acknowledged several limitations to the study. Unvaccinated people may have been less likely to test for COVID or use health services, with a possible underestimation of effects. Conversely, people with a diagnosis of COVID and related hospitalization may have been more likely to be diagnosed with mental illness in a hospital setting. It is also possible that the mental health effects observed were not unique to infection with SARS-CoV-2.

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